Background: The mechanisms of ischemic stroke in young adults are poorly understood. The main goal of the current investigation was to determine the possible contribution of genes affecting hemostasis, homocysteine metabolism and endothelial function on the occurrence of ischemic stroke in a cohort of young cases and corresponding controls. Methods: We evaluated in 97 consecutive patients referred to our center between April 2006 and July 2007 for a history of young adult ischemic stroke (age at first event, < 45 y) the prevalence of factor V Leiden, 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T and endothelial nitric oxide synthase (eNOS) 4ab gene variants. Ninety-nine subjects age and gender matched (18 to 45 y) from other departments of the Tiantan Hospital served as controls. Results: Homozygosity for the TT genotype of the MTHFR gene was 29 of 97 (29.9%) in patients and 34 of 99 (34.3%) in controls; this difference was not statistically significant (p > 0.05, χ2). Variation of factor V Leiden was not detected both in patients and in controls of this cohort. Genotype eNOS 4bb was 90 of 97 (92.8%) in patients and 81 of 99 (81.8%) in controls; this difference was statistically significant (p < 0.05, χ2 test). Conclusions: The eNOS 4ab variant appears to be an important risk factor for ischemic stroke in young Chinese population. © 2008 Elsevier B.V. All rights reserved.